Is single-dose amikacin (amikacin) sufficient as a full course of treatment for urinary tract infections (UTIs) in patients with impaired renal function, specifically end-stage renal disease (ESRD)?

Single-Dose Amikacin for UTIs in ESRD Patients

Single-dose amikacin is not recommended as a full course of treatment for urinary tract infections in patients with end-stage renal disease (ESRD) due to altered pharmacokinetics and insufficient evidence supporting this approach in complicated UTIs with impaired renal function. 1

Aminoglycosides in UTIs and Renal Impairment

• Aminoglycosides, including amikacin, are ideal agents for single-dose treatment of uncomplicated lower UTIs in patients with normal renal function due to their concentration-dependent bactericidal effect and prolonged urinary concentrations 1
• A meta-analysis of 13 studies with 13,804 patients found single-dose aminoglycoside treatment effective for lower UTIs with microbiologic cure rates of 87-100% in patients with normal renal function 1
• However, in ESRD patients, amikacin pharmacokinetics are significantly altered with half-life increasing from normal 2-3 hours to approximately 28-29 hours 2

Dosing Considerations in Renal Impairment

• In patients with ESRD, amikacin clearance is markedly reduced, requiring significant dosage adjustments 2, 3
• For patients on hemodialysis, the mean serum half-life of amikacin is approximately 3.75 hours during/after dialysis but extends to 28 hours when not on dialysis 2
• For patients on peritoneal dialysis, the half-life extends to approximately 29 hours 2
• Serial serum antibiotic concentrations are essential in ESRD patients to prevent cumulative toxicity 2

Guidelines for UTI Treatment in CRE and Renal Impairment

• Current guidelines provide specific recommendations for UTIs caused by resistant organisms:
  • For simple cystitis due to carbapenem-resistant Enterobacterales (CRE), single-dose aminoglycoside is recommended with a weak recommendation and very low quality of evidence 1
  • For complicated UTIs (cUTI), single-dose aminoglycoside is only recommended as an alternative regimen with weak recommendation and very low quality of evidence 1
  • There is insufficient evidence to support single-dose aminoglycoside for patients with complicated UTIs due to CRE 1

Risks and Monitoring in ESRD

• Amikacin use in ESRD carries significant risks of:
  • Ototoxicity (hearing loss) 1
  • Nephrotoxicity (further kidney damage) 1
• Monitoring requirements in ESRD patients:
  • Baseline audiogram and vestibular testing 1
  • Monthly assessment of renal function 1
  • Regular monitoring of serum drug concentrations 2
  • Assessment for auditory or vestibular symptoms 1

Alternative Treatment Options for UTIs in ESRD

• For complicated UTIs in patients with resistant organisms, guidelines recommend:
  • Ceftazidime-avibactam 2.5 g IV q8h (with dose adjustment for renal function) 1
  • Meropenem-vaborbactam or imipenem-cilastatin-relebactam (with dose adjustment) 1
  • Plazomicin 15 mg/kg IV q12h (with dose adjustment) 1

Clinical Approach to UTIs in ESRD

• For uncomplicated cystitis in ESRD patients:
  • Consider modified dosing of amikacin based on residual renal function 4
  • For stage 5 CKD on hemodialysis, a dose of 5 mg/kg every two days has been studied 4
  • For stage 5 CKD on peritoneal dialysis, a dose of 4 mg/kg every two days has been studied 4
• For complicated UTIs in ESRD patients:
  • Multi-dose regimens with careful monitoring are preferred over single-dose therapy 4
  • Every-day dosing appears more effective than every-two-days dosing in advanced CKD 4

Conclusion

While single-dose aminoglycoside therapy is effective for uncomplicated UTIs in patients with normal renal function, the altered pharmacokinetics in ESRD patients necessitate modified dosing strategies with careful monitoring. The evidence does not support using a single dose of amikacin as a full course of treatment for UTIs in ESRD patients.